ArticleThe Journal of biological chemistry2011
Biochemical impact of the host adaptation-associated PB2 E627K mutation on the temperature-dependent RNA synthesis kinetics of influenza A virus polymerase complex.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Pathogenicity and immune response of turkey A(H1N2) influenza virus of swine-origin on turkeys and mice.Veterinary research · 2026Article
- Avian influenza overview September-November 2025.EFSA journal. European Food Safety Authority · 2025Article
- LAIV Mutations Selectively Alter Influenza Viral RNA Polymerase Function, Favoring Transcription over Genome Synthesis.Viruses · 2025Article
- Avian influenza overview June-September 2025.EFSA journal. European Food Safety Authority · 2025Article
- Avian influenza overview March-June 2025.EFSA journal. European Food Safety Authority · 2025Article
- Immediate PB2-E627K amino acid substitution after single infection of highly pathogenic avian influenza H5N1 clade 2.3.4.4b in mice.Virology journal · 2025Article
- Inno4Vac Workshop Report Part 1: Controlled Human Influenza Virus Infection Model (CHIVIM) Strain Selection and Immune Assays for CHIVIM Studies, November 2021, MHRA, UK.Influenza and other respiratory viruses · 2024Review
- Molecular Markers and Mechanisms of Influenza A Virus Cross-Species Transmission and New Host Adaptation.Viruses · 2024Review
- Characterization of neurotropic HPAI H5N1 viruses with novel genome constellations and mammalian adaptive mutations in free-living mesocarnivores in Canada.Emerging microbes & infections · 2023Article
- SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility.Cell reports · 2023Article
- Non-Negligible Role of Trace Elements in Influenza Virus Infection.Metabolites · 2023Review
- Emergence of a Novel Reassortant H5N3 Avian Influenza Virus in Korean Mallard Ducks in 2018.Intervirology · 2022Article
- Real-Time Visualization of the Infection and Replication of a Mouse-Lethal Recombinant H9N2 Avian Influenza Virus.Frontiers in veterinary science · 2022Article
- Review
- Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Hemagglutinin Cleavability, Acid Stability, and Temperature Dependence Optimize Influenza B Virus for Replication in Human Airways.Journal of virology · 2019Article
- Secondary structure of the segment 5 genomic RNA of influenza A virus and its application for designing antisense oligonucleotides.Scientific reports · 2019Article
- Host and viral determinants of influenza A virus species specificity.Nature reviews. Microbiology · 2019Review
- The Multifaceted Zoonotic Risk of H9N2 Avian Influenza.Veterinary sciences · 2018Review
- Influenza virus segment 5 (+)RNA - secondary structure and new targets for antiviral strategies.Scientific reports · 2017Article
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4 authors.
Funding
Abstract
Most avian influenza A viruses, which preferentially replicate at the high temperatures found in the digestive tract of birds, have a glutamic acid at residue 627 of the viral RNA polymerase PB2 subunit (Glu-627), whereas the human viruses, which optimally replicate at the low temperatures observed in the human respiratory tract, have a lysine (Lys-627). The mechanism of action for this mutation is still not understood, although interaction with host factors has been proposed to play a major role. In this study, we explored an alternative, yet related, hypothesis that this PB2 mutation may alter the temperature-dependent enzymatic polymerase activity of the viral polymerase. First, the avian polymerase protein, which was purified from baculovirus expression system, indeed remained significantly active at higher temperatures (i.e. 37 and 42 °C), whereas the human E627K mutant drastically lost activity at these high temperatures. Second, our steady-state kinetics data revealed that the human E627K mutant polymerase is catalytically more active than the avian Glu-627 polymerase at 34 °C. Importantly, the E627K mutation elevates apparent K(cat) at low temperatures with little effect on K(m), suggesting that the E627K mutation alters the biochemical steps involved in enzyme catalysis rather than the interaction with the incoming NTP. Third, this temperature-dependent kinetic impact of the human E627K mutation was also observed with different RNA templates, with different primers and also in the presence of nucleoprotein. In conclusion, our study suggests that the amino acid sequence variations at residue 627 of PB2 subunit can directly alter the enzyme kinetics of influenza polymerase.
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